Search: onr:"swepub:oai:DiVA.org:uu-132386" >
In vitro ADMET and ...
In vitro ADMET and physicochemical investigations of poly-N-methylated peptides designed to inhibit Aβ aggregation
-
- Bose, Partha Pratim (author)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
-
- Chatterjee, Urmimala (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
-
- Hubatsch, Ina (author)
- Uppsala universitet,Institutionen för farmaci
-
show more...
-
- Artursson, Per (author)
- Uppsala universitet,Institutionen för farmaci,Institutionen för biokemi och organisk kemi
-
Govender, Thavendran (author)
-
Kruger, Hendrik G. (author)
-
Bergh, Margareta (author)
-
- Johansson, Jan (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
-
- Arvidsson, Per I. (author)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
-
show less...
-
(creator_code:org_t)
-
- Elsevier BV, 2010
- 2010
- English.
-
In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 18:16, s. 5896-5902
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
https://res.slu.se/i...
-
show less...
Abstract
Subject headings
Close
- N-Methylation is a common strategy for improving oral bioavailability of peptide-based lead structures. Herein, we present a detailed study on how the degree of N-methylation affects the absorption-distribution-metabolism-excretion-toxicity (ADMET) properties such as solubility, membrane transport, proteolytic stability, and general cell toxicity of the investigated peptides. As representative structures we chose hexapeptides 1-8. These peptides, corresponding to N-methylated analogues of residues 16-21 and 32-37 of the Abeta-peptide, pathological hallmark of Alzheimer's disease (AD), have previously been shown to inhibit aggregation of Abeta fibrils in vitro. This study suggests that poly-N-methylated peptides are non-toxic and have enhanced proteolytic stability over their non-methylated analogues. Furthermore, solubility in aqueous solution is seen to increase with increased degree of N-methylation, while membrane transport was found to be low for all investigated hexapeptides. The present results, together with those reported in the literature, suggest that poly-N-methylated peptides, especially shorter or equal to six residues, can be suitable candidates for drug design.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Alzheimer's disease
- Amyloid beta peptide
- N-Methylated peptide
- ADMET
- PHARMACY
- FARMACI
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database